Pulmonary embolism (PE) is still underdiagnosed even in hospitalized patients. In our recent experience, out of 92 postmortem cases of massive or submassive PE, only 28% were diagnosed before death, whereas the false-positives accounted only for 3% of cases. Similar conclusions have been drawn from large-scale autopsy studies performed in Norway and in the United States. The most important causes of an incorrect diagnosis are failure to suspect PE, and the protean nature of the disease. Remarkable differences actually exist concerning the point of origin and the final localization, as well as the size and age of thromboemboli, the presence or absence of pulmonary infarction, and the underlying pathology. Often a fatal embolus is relatively small but hardly tolerated because of the underlying cardiopulmonary situation. Attention should be called to the frequent autopsy finding of multiple PEs and pulmonary infarctions of apparently different age. This finding is important since it indicates that these patients suffered successive embolizations and the eventual death might have been prevented if an early diagnosis had been made.

The incidence of pulmonary thromboembolism is hard to assess by the pathologist as a result of seasonal variation of embolism and disappearance of emboli by thrombolysis. However, the great differences in estimates of the incidence in routine hospital autopsies is mainly related to variation in scrutiny of the investigation and in size of area searched microscopically. Obstruction of major pulmonary arteries almost always results from thromboembolism which is most often found in its acute stage. In chronic major vessel embolism, arterial obstruction by an organized mass may produce pulmonary hypertension. Recanalization of such a mass results in so-called bands and webs. There are no reliable criteria to differentiate between emboli and primary thrombi or their sequelae. In peripheral, particularly muscular pulmonary arteries, thrombi are most likely primary, especially when associated with advanced age and with pulmonary hypertension. However, small arteries may be subject to extensive microembolism following fragmentation of large thromboemboli. Thrombotic arteriopathy is the pulmonary arterial disease based upon either primary thrombosis or embolism. It is often associated with pulmonary hypertension, and characterized by irregular, nonlaminar, often obliterative, intimal fibrosis. Recanalization channels, sometimes widening to separate intravascular fibrous septa, are characteristic features. Reversibility of post-thrombotic lesions is very limited.

Even since the Surgeon General's 1964 report, the mortality rate from lung cancer has continued to rise. Although there is evidence that this continued increase in mortality will slow or level in the next decade, lung cancer mortality is a major health problem destined to remain with us for at least the next generation. There have been no established advances in the early detection or prevention of lung cancer in the last 30 years and our therapies have increased the cure rate only from 5 to 13% in this 30-year interval. Biologic advances have outpaced clinical advances in recent times and many of the advances are now ripe for clinical exploitation. There are currently more exciting clinical trials for all phases of lung cancer than at any time and it will be stimulating to witness the results of the clinical trials discussed herein. Hopefully, the results of these studies will lead to a decrease in lung cancer mortality in the next century, much as it increased in the past century.

Non-small lung cancer (NSCLC) is a disease that exhibits multiple genetic lesions. Lung Cancer Study Group (LCSG) 871 was designed to analyze this group of malignancies for alterations in growth factors and/or their receptors, oncogenes, tumor suppressor genes, and immediate early transcription factor genes. Immunohistochemical analysis showed that 32% of evaluable cases studied contained absent or abnormal Rb expression. Sequence analysis of the p53 gene revealed that 58% of these cancers contained structural alterations of this gene, whereas only 45% of these cases overexpressed p53 by immunohistochemical analysis. Finally, both Northern blot and immunohistochemical analysis showed that these tumors exhibited changes in the mRNA and protein expression levels respectively of the immediate early transcription factor genes c-fos, c-jun, and EGR, in that less expression of these genes was evident in the tumors compared with adjacent normal tissue. Understanding both the biologic and molecular significance of these findings may allow us to explore novel modalities for treatment of this disease.

Malignant pleural effusions are a common and significant problem in patients with advanced malignancies. In contrast to traditional sclerosing agents, intrapleural chemotherapy has the potential advantage of treating the underlying malignancy, in addition to treating the effusion. The Lung Cancer Study Group evaluated intrapleural cisplatin and cytarabine in patients with malignant pleural effusions from a variety of solid tumors. Forty-six patients with cytologically proven symptomatic and previously untreated malignant pleural effusions were entered. Cisplatin, as a single dose of 100 mg/m2, plus cytarabine 1,200 mg, were instilled into the pleural space via a chest tube that was then immediately removed. The overall response rate, complete plus partial at 3 weeks, was 49% (18/37 patients). One patient experienced reversible grade 3 renal toxic reactions, four patients had grade 3 hematologic toxic reactions, and five patients had grade 3 cardiopulmonary toxic reactions. Median length of response was 9 months for a complete remission and 5.1 months for a partial remission. Although chemotherapy has the potential advantage of treating the underlying malignancy in addition to controlling the malignant effusion, intracavitary cisplatin and cytarabine therapy as administered in this trial appears inferior to existing sclerosing agents for the control of malignant pleural effusions. Although administration is safe, it cannot be recommended for the standard control of malignant pleural effusions, but it may have a role incorporated into combination modality therapies for diseases such as malignant pleural mesothelioma.

In 1985 the Lung Cancer Study Group (LCSG) initiated clinical trials in malignant pleural mesothelioma because LCSG member institutions had access to large numbers of patients and had significant experience treating this uncommon cancer. The first trial, LCSG 851, defined the patient population seen by the LCSG, and the feasibility of performing surgical resection by extrapleural pneumonectomy in a multi-institutional setting. Of 83 patients entered on this study from September 1985 to June 1988, only 20 could undergo an extrapleural pneumonectomy, and 3 of 20 patients died postoperatively. This experience prompted the LCSG to explore combining a potentially less morbid operation, pleurectomy/decortication, with adjuvant therapy. The results of another LCSG trial (LCSG 861) and of a small single institutional pilot study demonstrated the feasibility of intrapleural cisplatin-based chemotherapy, and led to the development of LCSG 882, which combined pleurectomy/decortication with postoperative intrapleural, and subsequent systemic, cisplatin-based chemotherapy. This study was not completed because of discontinuation of funding for the LCSG. However, a single-institution phase 2 trial of very similar design has subsequently shown the feasibility of this combined modality approach.

Any program of therapy for clinically advanced non-small cell lung cancer (NSCLC) that would increase the incidence of local tumor control and decrease the likelihood of distant metastatic disease would be of obvious benefit. The objective of neoadjuvant therapy is to eradicate the primary tumor and micrometastatic disease. In the past 10 years, many trials have been completed to evaluate neoadjuvant therapy and they have included sequential chemoradiotherapy, concurrent chemoradiotherapy, chemotherapy/surgery, and chemoradiation/surgery. These trials have predominately been phase 2 trials and have demonstrated that chemotherapy is generally well tolerated, surgery is technically feasible, and operative morbidity and mortality are not excessive. Long-term survival for patients with clinically advanced NSCLC is improved when compared with historic controls. These trials have demonstrated a greater than 50% clinical response rate and in approximately 20% of patients who have undergone resections, the tumor is sterilized. This latter group of patients demonstrate significantly improved survival. Cost-benefit ratios and quality of life have yet to be evaluated. Final determination of the effectiveness of neoadjuvant therapy for NSCLC awaits completion of phase 3 trials.

There have been no major breakthroughs in surgical management for primary lung cancer during the past 40 years. Improved 5-year survival relates primarily to improved preoperative staging and appropriate selection of patients for resection. Perioperative morbidity and mortality, however, has been significantly reduced. Certain principles pertain to current surgical management: resection remains the best treatment for patients with localized, non-small cell primary lung cancer. Accurate preoperative diagnosis and staging: whenever possible, it is desirable to establish the diagnosis and cell type before operation. Accurate evaluation of the N status warrants wide application of invasive staging with mediastinoscopy or a variant. Indications for resection: only patients in whom a complete resection is anticipated should be selected for surgery. Such cases included T1 to T4 stages, N0 and N1 tumors, and selected N2 cases. The indication for resection in patients with hematogenous metastases are anecdotal. Intraoperative staging: accurate and deliberate intraoperative staging with evaluation of nodes using the American Thoracic Society map is highly desirable. The nature of nodal metastases exerts a critical influence on prognosis and in the selection of patients for surgical resection. At present, there is no clear indication for adjuvant therapy in surgically resected cases other than for evaluation and clinical trials.

In the late 1970s and early 1980s, the Lung Cancer Study Group conducted a series of adjuvant chemotherapy trials in patients with resected non-small cell lung cancer. Although some of these trials yielded modest survival benefit, the length of improved survival essentially equaled the time spent receiving chemotherapy. Consequently, few physicians routinely employ postoperative chemotherapy in spite of its theoretical appeal. Possible explanations for the failure of adjuvant chemotherapy to provide meaningful prolongation of survival in non-small cell lung cancer include lack of effective chemotherapy, incorrect chemotherapy regimen, inadequate dose intensity, and possibly inadequate trial design. Future postoperative adjuvant trials should focus on treating patients with resected early stage lesions (T1N1, T2N1, T2N0). What role, if any, newer antineoplastic agents will play in the postoperative setting remains to be determined. Neoadjuvant induction chemotherapy may well prove to be a superior treatment strategy and deserves further investigation.

Acute myocardial infarction is the result of an acute interruption of myocardial blood flow resulting in ischemic myocardial necrosis. The pathogenesis of this phenomenon nearly always involves acute thrombosis superimposed on a disrupted atherosclerotic plaque. Thrombolytic agents have been conclusively shown to reduce mortality in many patient subgroups with myocardial infarction, including the elderly, patients with inferior myocardial infarction, and patients with systolic hypertension. Nearly all patients with acute myocardial infarction of less than 6 h in duration with S-T segment elevation should receive thrombolysis unless significant contraindications exist and outweigh the potential benefits. Aspirin should be given to almost all patients regardless of whether they receive thrombolysis. Angioplasty and coronary artery bypass surgery are useful as primary or secondary modes of reperfusion in selected patients with infarction.

We describe a case of unsuspected infrahepatic interruption of the inferior vena cava with hemiazygos continuation in a 67-year-old man presenting with chest pain and evidence of mitral regurgitation. He had no persistent superior vena cava, with the hemiazygos draining directly into the right superior vena cava. Polysplenia and severe mitral prolapse were also present: the latter may represent more than an incidental finding in this condition. This malformation may deserve consideration in adults undergoing femoral right heart catheterization. Chest radiographic studies are the basic clue to the diagnosis.

A 68-year-old man developed fever, cough, and dyspnea after intravesical bacillus Calmette-Guerin (BCG). Chest radiograph revealed diffuse reticulonodular infiltrates with caseating granulomas on transbronchial biopsy specimen. Cultures were negative and the patient's condition improved with corticosteroids. The mechanism for BCG-induced granulomatous inflammation is poorly understood. Optimal therapy includes corticosteroids.

We report a case of 63-year-old man who developed massive pulmonary hemorrhage following intravenous streptokinase for acute myocardial infarction. Pulmonary hemorrhage was diagnosed by the triad of hemoptysis, a drop in hematocrit, and a new unilateral infiltrate on chest radiograph. This diagnosis was confirmed by autopsy findings. Pulmonary hemorrhage has rarely been reported following thrombolytic therapy. We believe that pulmonary hemorrhage is a rare but a potentially life-threatening complication of thrombolytic therapy and should be considered in the differential diagnosis of pulmonary infiltrates or falling hemoglobin after thrombolytic therapy for acute myocardial infarction with no obvious site of bleeding.

Takayasu's arteritis is an uncommon condition affecting predominantly young women. Because the disorder affects women in childbearing age, it may be recognized the first time during pregnancy. Various cardiovascular events may occur in the perinatal period. We describe a patient with Takayasu's arteritis who presented with massive hemoptysis. To our knowledge, this manifestation has not been documented previously.

Delayed-onset pericardial effusion following coronary artery bypass grafts can give rise to significant morbidity in its presentation and in its management by traditional surgical techniques. A video-assisted thoracoscopic technique to create a pericardial window, with the advantage of a minimally invasive approach combined with excellent visualization in such a patient is described.

Pleural effusion represents an unusual but significant manifestation of actinomycosis, as illustrated in this case presentation. The diagnosis was made after bronchoscopy and examination of bronchoalveolar fluid and culture. No parenchymal abnormality was noted on the chest film.